Yes-associated protein (YAP) is a transcriptional co-activator that regulates cell proliferation and survival by binding to a select set of enhancers for target gene activation. How YAP coordinates these transcriptional responses is unknown. Here, we demonstrate that YAP forms liquid-like condensates in the nucleus. Formed within seconds of hyperosmotic stress, YAP condensates compartmentalized the YAP transcription factor TEAD1 and other YAP-related co-activators, including TAZ, and subsequently induced the transcription of YAP-specific proliferation genes. Super-resolution imaging using assay for transposase-accessible chromatin with photoactivated localization microscopy revealed that the YAP nuclear condensates were areas enriched in accessible chromatin domains organized as super-enhancers. Initially devoid of RNA polymerase II, the accessible chromatin domains later acquired RNA polymerase II, transcribing RNA. The removal of the intrinsically-disordered YAP transcription activation domain prevented the formation of YAP condensates and diminished downstream YAP signalling. Thus, dynamic changes in genome organization and gene activation during YAP reprogramming is mediated by liquid-liquid phase separation.

中文翻译：

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YAP 的相分离重组基因组拓扑结构以实现长期 YAP 靶基因表达。

Yes 相关蛋白 (YAP) 是一种转录共激活因子，它通过与一组选定的增强子结合以激活靶基因来调节细胞增殖和存活。YAP 如何协调这些转录反应尚不清楚。在这里，我们证明 YAP 在细胞核中形成液体状凝聚物。在高渗应激的几秒钟内形成，YAP 凝聚物将 YAP 转录因子 TEAD1 和其他 YAP 相关共激活因子（包括 TAZ）区分开来，随后诱导 YAP 特异性增殖基因的转录。使用光激活定位显微镜检测转座酶可接近染色质的超分辨率成像显示，YAP 核凝聚物是富含可接近染色质结构域的区域，组织为超级增强剂。最初没有 RNA 聚合酶 II，可接近的染色质结构域后来获得了 RNA 聚合酶 II，转录 RNA。内在无序的 YAP 转录激活域的去除阻止了 YAP 凝聚物的形成并减少了下游 YAP 信号传导。因此，YAP 重编程过程中基因组组织和基因激活的动态变化是由液-液相分离介导的。